This rare genetic condition, inherited in a dominant autosomal fashion, where one copy of the p53 gene is inactivated in the germline, dramatically increases the risk for developing a number of malignancies, such as breast cancer, brain cancer, leukemia, soft tissue sarcomas etc. Risk is mediated by the relatively high probability of a “second hit” and inactivation of the remaining p53 allele due to environmental factors, which is sufficient to trigger malignant transformation. The gene discussed is TP53; the disease is soft tissue sarcoma.